The long-term objectives are a better understanding of why the pulmonary artery vasoconstricts in response to hypoxia. Hypoxic pulmonary vasoconstriction (HPV) occurs in both normal and diseased lungs and is an important component of chronic respiratory diseases and shock lung. The pulmonary hypertension consequent to this vasoconstriction often becomes an important part of the pathophysiology. While sympathetic nerves appear not to be essential for HPV to occur, the noradrenergic system appears to be capable of fine tuning the response and our studies have shown that norepinephrine (NE) dynamics at neuroeffector junctions are different in pulmonary artery than in coronary artery or in saphenous vein and are, in addition, changed during acute or chronic hypoxia in a direction which increases the availability of NE in synaptic clefts. Studies are now proposed: (1) to determine whether differences in the regulation of NE levels in synaptic clefts in pulmonary artery compared to saphenous vein are a unique feature of pulmonary artery or simply represent differences between artery and vein; (2) to determine whether the cotransmitter peptide, neuropeptide Y (NPY), which typically enhances vasoconstrictor responses, or the peptide, vasoactive intestinal polypeptide (VIP), which typically enhances vasodilator responses may influence NE dynamics or effector responses at neuroeffector units in pulmonary artery; (3) to determine whether hypoxia or the volatile anesthetic agent halothane alters the interaction bf NPY, VIP or NE at neuroeffector junctions in pulmonary or systemic arteries. Techniques to be used include: superfused, isolated, helically cut strips of blood vessel in which postganglionic nerves can be stimulated electrically, the superfusate (and the tissue) analyzed for endogenous NE using liquid chromatography with electrochemical detection and for NPY and VIP using radioimmunoassay technique; isolated organ bath studies using rings of pulmonary and systemic arteries in which the postjunctional actions of VIP and NPY will be determined during high and low oxygen tensions and during halothane. An understanding of the interactions between NE and peptides that occur at neuroeffector units during normoxia and why these change during hypoxia may open new avenues of therapy directed at pulmonary hypertension.